Otto Wolfgang, Breyer Johannes, Herdegen Sonja, Eder Fabian, Bertz Simone, May Matthias, Mayr Roman, Lausenmeyer Eva M, Denzinger Stefan, van Rhijn Bas W G, Burger Maximilian, Hartmann Arndt
Department of Urology, University of Regensburg, Landshuterstr. 65, 93053, Regensburg, Germany.
Institute of Pathology, University of Regensburg, Regensburg, Germany.
Int Urol Nephrol. 2017 Mar;49(3):431-437. doi: 10.1007/s11255-016-1491-9. Epub 2016 Dec 29.
Stage pT1 urothelial bladder cancer (UBC) is characterized as a challenging subentity of urothelial carcinoma with an unforeseeable clinical course. In addition to more or less established clinical and histopathological features, we evaluated the role of epithelial-mesenchymal transition (EMT) marker E-cadherin, shown to be of prognostic value in muscle-invasive disease, regarding the prognosis of stage pT1 high-grade (hg) UBC.
Tissue of 226 stage pT1 hg UBC patients from transurethral resection could be immunostained for E-cadherin. Kaplan-Meier analysis and univariate and multivariate Cox regression analyses regarding progression-free (PFS) and cancer-specific survival (CSS) were performed.
Aberrant expression of E-cadherin was recognized in 74% of patients. Kaplan-Meier analysis showed that aberrant E-cadherin expression was associated with worse 10-year PFS (62 vs. 90%, p = 0.045). In univariate analysis, aberrant E-cadherin staining, associated carcinoma in situ, grading 3 after WHO classification 1973 and infiltrative growth pattern at the invasion front were the statistically significant predictive factors for worse PFS, only infiltrative growth pattern for CSS. With regard to progression, grading 3 after WHO classification of 1973 (HR 6.49; CI 1.54-27.28, p = 0.011) and infiltrative tumor invasion pattern (HR 2.06; CI 1.10-3.86, p = 0.024) revealed as independent factors for PFS, and there was a trend also for E-cadherin expression (HR 0.45; CI 0.19-1.06; p = 0.068). Regarding CSS, infiltrative tumor growth pattern (HR 3.79; CI 1.67-8.60, p = 0.001) was the only statistically significantly independent predictive factor in multivariate Cox regression analysis.
Beside invasion growth pattern and WHO grading 1973 that achieved to be independent prognostic factors, there was a trend for the parameter E-cadherin expression to be of predictive value for PFS in stage pT1 hg urothelial bladder carcinoma after organ-sparing approach. Further studies on genetic level are warranted to define the distinct role of EMT in early-invasive UBC.
pT1期尿路上皮膀胱癌（UBC）是尿路上皮癌中一个具有挑战性的亚实体，其临床病程不可预测。除了或多或少已确定的临床和组织病理学特征外，我们评估了上皮-间质转化（EMT）标志物E-钙黏蛋白在pT1期高级别（hg）UBC预后中的作用，该标志物在肌层浸润性疾病中已显示具有预后价值。
对226例经尿道切除术的pT1期hg UBC患者的组织进行E-钙黏蛋白免疫染色。进行了无进展生存期（PFS）和癌症特异性生存期（CSS）的Kaplan-Meier分析以及单因素和多因素Cox回归分析。
74%的患者存在E-钙黏蛋白异常表达。Kaplan-Meier分析显示，E-钙黏蛋白异常表达与较差的10年PFS相关（62%对90%，p = 0.045）。在单因素分析中，E-钙黏蛋白染色异常、伴发原位癌、1973年WHO分类后3级以及浸润前沿的浸润性生长模式是PFS较差的统计学显著预测因素，CSS方面只有浸润性生长模式是显著因素。关于进展，1973年WHO分类后3级（HR 6.49；CI 1.54 - 27.28，p = 0.011）和浸润性肿瘤侵袭模式（HR 2.06；CI 1.10 - 3.86，p = 0.024）是PFS的独立因素，E-钙黏蛋白表达也有此趋势（HR 0.45；CI 0.19 - 1.06；p = 0.068）。关于CSS，浸润性肿瘤生长模式（HR 3.79；CI 1.67 - 8.60，p = 0.001）是多因素Cox回归分析中唯一具有统计学显著意义的独立预测因素。
除了浸润性生长模式和1973年WHO分级成为独立的预后因素外，在保留器官治疗后的pT1期hg尿路上皮膀胱癌中，E-钙黏蛋白表达参数对PFS具有预测价值的趋势。有必要在基因水平进行进一步研究以明确EMT在早期浸润性UBC中的独特作用。
